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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">mrj</journal-id><journal-title-group><journal-title xml:lang="ru">Современная ревматология</journal-title><trans-title-group xml:lang="en"><trans-title>Modern Rheumatology Journal</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1996-7012</issn><issn pub-type="epub">2310-158X</issn><publisher><publisher-name>IMA-PRESS, LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.14412/1996-7012-2021-4-38-42</article-id><article-id custom-type="elpub" pub-id-type="custom">mrj-1168</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL INVESTIGATIONS</subject></subj-group></article-categories><title-group><article-title>Опыт эффективного использования ингибиторов интерлейкина 6 у больных анкилозирующим спондилитом со вторичным амилоидозом</article-title><trans-title-group xml:lang="en"><trans-title>A case of effective use of interleukin 6 inhibitors in patients with ankylosing spondylitis with secondary amyloidosis</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3195-5187</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Эрдес</surname><given-names>Ш. Ф.</given-names></name><name name-style="western" xml:lang="en"><surname>Erdes</surname><given-names>Sh. F.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шандор Федорович Эрдес</p><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>Shandor Fedorovich Erdes</p><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><email xlink:type="simple">123456_57@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-1684-1213</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Румянцева</surname><given-names>Д. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Rumyantseva</surname><given-names>D. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2246-686X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Агафонова</surname><given-names>Е. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Agafonova</surname><given-names>E. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9755-5760</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Урумова</surname><given-names>М. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Urumova</surname><given-names>M. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3173-773X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Старкова</surname><given-names>А. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Starkova</surname><given-names>A. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-4505-0162</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Красненко</surname><given-names>С. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Krasnenko</surname><given-names>S. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>115522, Москва, Каширское шоссе, 34А</p></bio><bio xml:lang="en"><p>34A, Kashirskoe Shosse, Moscow 115522</p></bio><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>ФГБНУ «Научно-исследовательский институт ревматологии им. В.А. Насоновой»</institution><country>Россия</country></aff><aff xml:lang="en"><institution>V.A. Nasonova Research Institute of Rheumatology</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2021</year></pub-date><pub-date pub-type="epub"><day>14</day><month>08</month><year>2021</year></pub-date><volume>15</volume><issue>4</issue><fpage>38</fpage><lpage>42</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Эрдес Ш.Ф., Румянцева Д.Г., Агафонова Е.М., Урумова М.М., Старкова А.С., Красненко С.О., 2021</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="ru">Эрдес Ш.Ф., Румянцева Д.Г., Агафонова Е.М., Урумова М.М., Старкова А.С., Красненко С.О.</copyright-holder><copyright-holder xml:lang="en">Erdes S.F., Rumyantseva D.G., Agafonova E.M., Urumova M.M., Starkova A.S., Krasnenko S.O.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://mrj.ima-press.net/mrj/article/view/1168">https://mrj.ima-press.net/mrj/article/view/1168</self-uri><abstract><p>В рандомизированных клинических исследованиях, в которых изучалась эффективность ингибиторов интерлейкина 6 (иИЛ6) тоцилизумаба (ТЦЗ) и сарилимумаба при анкилозирующем спондилите (АС), показана их неэффективность. Однако имеются многочисленные данные о том, что ИЛ6 активно участвует в патогенезе данного заболевания. Кроме того, установлена эффективность иИЛ6 у пациентов со вторичным АА-амилоидозом.Цель исследования – проанализировать результаты назначения ТЦЗ при АС, осложненном вторичным АА-амилоидозом. Пациенты и методы. В анализ включено 6 больных АС со вторичным АА-амилоидозом. Все пациенты были мужского пола, позитивные по HLA-B27. Средний возраст больных составил 44±9,2 года, средний возраст дебюта болезни – 16,3±7,9 года, средняя длительность АС – 26,0±7,5 года. Все 6 пациентов имели гистологически подтвержденный вторичный АА-амилоидоз: у всех отмечалось поражение почек, у 5 – также поражение желудочно-кишечного тракта и у 2 – сердца. В качестве первого биологического препарата ТЦЗ был назначен 2 больным, а 4 пациента ранее уже получали один или более ингибитор фактора некроза опухоли α. Средняя длительность лечения ТЦЗ составила 27,6 [3,0; 36,0] мес.Результаты и обсуждение. На фоне терапии ТЦЗ значимо снизились как уровень СРБ (М±σ): с 81,1±74,5 до 1,2±0,8 мг/л (р&lt;0,05) и суточной протеинурии (Ме [25-й; 75-й перцентили]): с 1,8 [1,0; 2,1] до 0,2 [0,1; 0,3] г/сут (р&lt;0,05), так и индексы активности АС – BASDAI (М±σ): с 6,2±1,6 до 3,3±0,9 (р&lt;0,05); ASDAS-СРБ (М±σ) с 4,6±1,1 до 2,04±0,7 (р&lt;0,05). Положительная динамика отмечена и в отношении уменьшения числа больных с воспалительной болью в спине, артритами и кокситом. Описан клинический случай применения ТЦЗ с развитием клинико-лабораторной ремиссии АС.Заключение. Представленные данные показывают, что в определенных клинических ситуациях иИЛ6 могут быть высокоэффективны при АС.</p></abstract><trans-abstract xml:lang="en"><p>Ineffectiveness of interleukin 6 inhibitors (iIL6), tocilizumab (TCZ) and sarilimumab in ankylosing spondylitis (AS) was shown in randomized clinical trials. However, there is ample evidence that IL6 is actively involved in the pathogenesis of this disease. In addition, the efficacy of iIL6 in patients with secondary AA-amyloidosis was established.Objective: to analyze the results of TCZ administration in AS, complicated by secondary AA-amyloidosis.Patients and methods. The analysis included 6 patients with AS with secondary AA-amyloidosis. All patients were HLA-B27 positive male. The average age of patients was 44±9.2 years, the average age of the disease onset was 16.3±7.9 years, the average duration of AS was 26.0±7.5 years. All 6 patients had pathomorphologic confirmed secondary AA-amyloidosis: all had kidney affection, 5 patients also had gastrointestinal tract affection and 2 had heart affection. As a first biological drug TCZ was prescribed in 2 patients, and 4 patients had previously received one or more inhibitors of tumor necrosis factor α. The average duration of TCZ treatment was 27.6 [3.0; 36.0] months.Results and discussion. During TCZ therapy, the level of CRP (M±σ) significantly decreased: from 81.1±74.5 to 1.2±0.8 mg/L (p&lt;0.05), as well as daily proteinuria (Me [25th ; 75th percentile]): from 1.8 [1.0; 2.1] to 0.2 [0.1; 0.3] g/day (p&lt;0.05) and AS activity indices – BASDAI (M±σ): from 6.2±1.6 to 3.3±0.9 (p&lt;0.05 ); ASDAS-CRP (M±σ) from 4.6±1.1 to 2.04±0.7 (p&lt;0.05). Positive dynamics was also noted in relation to a decrease in the number of patients with inflammatory back pain, arthritis and coxitis. A case of clinical and laboratory remission of AS on TCZ treatment is described. Conclusion. The presented data show that in certain clinical situations iIL6 can be highly effective in AS.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>анкилозирующий спондилит</kwd><kwd>вторичный АА-амилоидоз</kwd><kwd>ингибиторы ИЛ6</kwd><kwd>тоцилизумаб</kwd></kwd-group><kwd-group xml:lang="en"><kwd>ankylosing spondylitis</kwd><kwd>secondary AA-amyloidosis</kwd><kwd>IL6 inhibitors</kwd><kwd>tocilizumab</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование выполнено в рамках поисковой научной темы НИОКР №АААА А20-120041390035-8.</funding-statement><funding-statement xml:lang="en">The investigation has been conducted within scientific practical-research topic №АААА А20-120041390035-8.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Limon-Camacho L, Vargas-Rojas MI, VazquezMellado J, et al. In vivo peripheral blood proinяammatory T cells in patients with ankylosing spondylitis. J Rheumatol. 2012 Apr;39(4):830-5. doi: 10.3899/jrheum.110862. Epub 2012 Feb 15.</mixed-citation><mixed-citation xml:lang="en">Limon-Camacho L, Vargas-Rojas MI, VazquezMellado J, et al. In vivo peripheral blood proinяammatory T cells in patients with ankylosing spondylitis. J Rheumatol. 2012 Apr;39(4):830-5. doi: 10.3899/jrheum.110862. Epub 2012 Feb 15.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Mattey DL, Packham JC, Nixon NB, et al. Association of cytokine and matrix metalloproteinase profles with disease activity and function in ankylosing spondylitis. Arthritis Res Ther. 2012 May 28;14(3):R127. doi: 10.1186/ar3857.</mixed-citation><mixed-citation xml:lang="en">Mattey DL, Packham JC, Nixon NB, et al. Association of cytokine and matrix metalloproteinase profles with disease activity and function in ankylosing spondylitis. Arthritis Res Ther. 2012 May 28;14(3):R127. doi: 10.1186/ar3857.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Suzuki T, Yoshinaga N, Tanabe S. Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem. 2011 Sep 9; 286(36):31263-71. doi: 10.1074/jbc.M111.238147. Epub 2011 Jul 19.</mixed-citation><mixed-citation xml:lang="en">Suzuki T, Yoshinaga N, Tanabe S. Interleukin-6 (IL-6) regulates claudin-2 expression and tight junction permeability in intestinal epithelium. J Biol Chem. 2011 Sep 9; 286(36):31263-71. doi: 10.1074/jbc.M111.238147. Epub 2011 Jul 19.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010 Jul;40(7):1830-5. doi: 10.1002/eji.201040391.</mixed-citation><mixed-citation xml:lang="en">Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol. 2010 Jul;40(7):1830-5. doi: 10.1002/eji.201040391.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Chalaris A, Garbers C, Rabe B, et al. The soluble Interleukin 6 receptor: generation and role in inяammation and cancer. Eur J Cell Biol. Jun-Jul 2011;90(6-7):484-94. doi: 10.1016/j.ejcb.2010.10.007. Epub 2010 Dec 8.</mixed-citation><mixed-citation xml:lang="en">Chalaris A, Garbers C, Rabe B, et al. The soluble Interleukin 6 receptor: generation and role in inяammation and cancer. Eur J Cell Biol. Jun-Jul 2011;90(6-7):484-94. doi: 10.1016/j.ejcb.2010.10.007. Epub 2010 Dec 8.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, Александрова ЕН, Авдеева АС, Панасюк ЕЮ. Ингибиция интерлейкина 6 – новые возможности фармакотерапии иммуновоспалительных ревматических заболеваний. Научно-практическая ревматология. 2013;51(4):416-27.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, Aleksandrova EN, Avdeeva AS, Panasyuk EYu. Interleukin 6 inhibition – new possibilities of pharmacotherapy of immunoinflammatory rheumatic diseases. Nauchnoprakticheskaya revmatologiya. 2013;51(4): 416-27. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Londono J, Romero-Sanchez MC, Torres VG, et al. The association between serum levels of potential biomarkers with the presence of factors related to the clinical activity and poor prognosis in spondyloarthritis. Rev Bras Reumatol. 2012 Aug;52(4):536-44.</mixed-citation><mixed-citation xml:lang="en">Londono J, Romero-Sanchez MC, Torres VG, et al. The association between serum levels of potential biomarkers with the presence of factors related to the clinical activity and poor prognosis in spondyloarthritis. Rev Bras Reumatol. 2012 Aug;52(4):536-44.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest. 2011 Sep;121(9):3375-83. doi: 10.1172/JCI57158. Epub 2011 Sep 1.</mixed-citation><mixed-citation xml:lang="en">Jones SA, Scheller J, Rose-John S. Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling. J Clin Invest. 2011 Sep;121(9):3375-83. doi: 10.1172/JCI57158. Epub 2011 Sep 1.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Tanaka T, Kishimoto T. Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases. Int J Biol Sci. 2012;8(9):1227-36. doi: 10.7150/ijbs.4666. Epub 2012 Oct 24.</mixed-citation><mixed-citation xml:lang="en">Tanaka T, Kishimoto T. Targeting Interleukin-6: All the Way to Treat Autoimmune and Inflammatory Diseases. Int J Biol Sci. 2012;8(9):1227-36. doi: 10.7150/ijbs.4666. Epub 2012 Oct 24.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97. doi: 10.1016/S0140-6736(08)60453-5.</mixed-citation><mixed-citation xml:lang="en">Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis (OPTION study): a double-blind, placebo-controlled, randomised trial. Lancet. 2008 Mar 22;371(9617):987-97. doi: 10.1016/S0140-6736(08)60453-5.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ. Применение тоцилизумаба при ревматоидном артрите: новые данные. Научно-практическая ревматология. 2011;(6):46-56.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL. The use of tocilizumab in rheumatoid arthritis: new data. Nauchnoprakticheskaya revmatologiya. 2011;(6):46-56. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Gossec L, Del CAstillo-Pinol N, Roux C, Dougados M. Lack of efficacy of tocilizumab in severe axial refractory spondyloarthritis: a report of 5 patients. Clin Exp Rheumatol. SepOct 2012;30(5):805. Epub 2012 Oct 17.</mixed-citation><mixed-citation xml:lang="en">Gossec L, Del CAstillo-Pinol N, Roux C, Dougados M. Lack of efficacy of tocilizumab in severe axial refractory spondyloarthritis: a report of 5 patients. Clin Exp Rheumatol. SepOct 2012;30(5):805. Epub 2012 Oct 17.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Sieper J, Porter-Brown B, Thompson L, et al. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis. 2014 Jan; 73(1):95-100. doi: 10.1136/annrheumdis2013-203559. Epub 2013 Jun 13.</mixed-citation><mixed-citation xml:lang="en">Sieper J, Porter-Brown B, Thompson L, et al. Assessment of short-term symptomatic efficacy of tocilizumab in ankylosing spondylitis: results of randomised, placebo-controlled trials. Ann Rheum Dis. 2014 Jan; 73(1):95-100. doi: 10.1136/annrheumdis2013-203559. Epub 2013 Jun 13.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Sieper J, Braun J, Kay J, et al. Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis. 2015 Jun;74(6):1051-7. doi: 10.1136/annrheumdis-2013-204963. Epub 2014 Feb 18.</mixed-citation><mixed-citation xml:lang="en">Sieper J, Braun J, Kay J, et al. Sarilumab for the treatment of ankylosing spondylitis: results of a Phase II, randomised, double-blind, placebo-controlled study (ALIGN). Ann Rheum Dis. 2015 Jun;74(6):1051-7. doi: 10.1136/annrheumdis-2013-204963. Epub 2014 Feb 18.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Ugurlu S, Hacioglu A, Adibnia Y, et al. Tocilizumab in the treatment of twelve cases with aa amyloidosis secondary to familial mediterranean fever. Orphanet J Rare Dis. 2017 May 30;12(1):105. doi: 10.1186/s13023-017-0642-0.</mixed-citation><mixed-citation xml:lang="en">Ugurlu S, Hacioglu A, Adibnia Y, et al. Tocilizumab in the treatment of twelve cases with aa amyloidosis secondary to familial mediterranean fever. Orphanet J Rare Dis. 2017 May 30;12(1):105. doi: 10.1186/s13023-017-0642-0.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Yilmaz S, Tekgäz E, Cinar M. Recurrence of proteinuria after cessation of tocilizumab in patients with AA amyloidosis secondary to FMF. Eur J Rheumatol. 2018 Dec; 5(4):278-80. doi: 10.5152/eurjrheum.2018.17183. Epub 2018 Jul 20.</mixed-citation><mixed-citation xml:lang="en">Yilmaz S, Tekgäz E, Cinar M. Recurrence of proteinuria after cessation of tocilizumab in patients with AA amyloidosis secondary to FMF. Eur J Rheumatol. 2018 Dec; 5(4):278-80. doi: 10.5152/eurjrheum.2018.17183. Epub 2018 Jul 20.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Насонов ЕЛ, Лила АМ. Ингибиция интерлейкина 6 при иммуновоспалительных ревматических заболеваниях: достижения, перспективы и надежды. Научно-практическая ревматология. 2017; 55(6):590-9.</mixed-citation><mixed-citation xml:lang="en">Nasonov EL, Lila AM. Interleukin 6 inhibition in immuno-inflammatory rheumatic diseases: achievements, prospects and hopes. Nauchno-prakticheskaya revmatologiya. 2017; 55(6):590-9. (In Russ.).</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Tutuncu ZN, Bilgie A, Kennedy LG, et al. Interleukin-6, acute phase reactants and clinical status in ankylosing spondylitis. Ann Rheum Dis. 1994;53:425-6.</mixed-citation><mixed-citation xml:lang="en">Tutuncu ZN, Bilgie A, Kennedy LG, et al. Interleukin-6, acute phase reactants and clinical status in ankylosing spondylitis. Ann Rheum Dis. 1994;53:425-6.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Gratacos J, Collado A, Filella X, et al. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol. 1994 Oct;33(10):927-31. doi: 10.1093/rheumatology/33.10.927.</mixed-citation><mixed-citation xml:lang="en">Gratacos J, Collado A, Filella X, et al. Serum cytokines (IL-6, TNF-alpha, IL-1 beta and IFN-gamma) in ankylosing spondylitis: a close correlation between serum IL-6 and disease activity and severity. Br J Rheumatol. 1994 Oct;33(10):927-31. doi: 10.1093/rheumatology/33.10.927.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Bal A, Unlu E, Bahar G, et al. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol. 2007 Feb;26(2):211-5. doi: 10.1007/s10067-006-0283-5. Epub 2006 Apr 1.</mixed-citation><mixed-citation xml:lang="en">Bal A, Unlu E, Bahar G, et al. Comparison of serum IL-1 beta, sIL-2R, IL-6, and TNF-alpha levels with disease activity parameters in ankylosing spondylitis. Clin Rheumatol. 2007 Feb;26(2):211-5. doi: 10.1007/s10067-006-0283-5. Epub 2006 Apr 1.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Visvanathan S, Wagner C, Marini JC, et al. Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab. Ann Rheum Dis. 2008 Apr;67(4): 511-7. doi: 10.1136/ard.2007.071605. Epub 2007 Jul 20.</mixed-citation><mixed-citation xml:lang="en">Visvanathan S, Wagner C, Marini JC, et al. Inflammatory biomarkers, disease activity and spinal disease measures in patients with ankylosing spondylitis after treatment with infliximab. Ann Rheum Dis. 2008 Apr;67(4): 511-7. doi: 10.1136/ard.2007.071605. Epub 2007 Jul 20.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Visvanathan S, van der Heijde D, Deodhar A, et al. Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis. 2009 Feb;68(2):175-82. doi: 10.1136/ard.2007.084426. Epub 2008 May 21.</mixed-citation><mixed-citation xml:lang="en">Visvanathan S, van der Heijde D, Deodhar A, et al. Effects of infliximab on markers of inflammation and bone turnover and associations with bone mineral density in patients with ankylosing spondylitis. Ann Rheum Dis. 2009 Feb;68(2):175-82. doi: 10.1136/ard.2007.084426. Epub 2008 May 21.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Wendling D, Racadot E, Toussirot E, Wijdenes J. Combination therapy of antiCD4 and anti-IL6 monoclonal antibodies in a case of severe spondylarthropathy. Br J Rheumatol. 1996 Dec;35(12):1330. doi: 10.1093/rheumatology/35.12.1330.</mixed-citation><mixed-citation xml:lang="en">Wendling D, Racadot E, Toussirot E, Wijdenes J. Combination therapy of antiCD4 and anti-IL6 monoclonal antibodies in a case of severe spondylarthropathy. Br J Rheumatol. 1996 Dec;35(12):1330. doi: 10.1093/rheumatology/35.12.1330.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Henes JC, Horger M, Guenaydin I, et al. Mixed response to tocilizumab for ankylosing spondylitis. Ann Rheum Dis. 2010 Dec;69(12): 2217-8. doi: 10.1136/ard.2009.126706. Epub 2010 Jun 4.</mixed-citation><mixed-citation xml:lang="en">Henes JC, Horger M, Guenaydin I, et al. Mixed response to tocilizumab for ankylosing spondylitis. Ann Rheum Dis. 2010 Dec;69(12): 2217-8. doi: 10.1136/ard.2009.126706. Epub 2010 Jun 4.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Wendling D, Bossert M, Prati C. Short-term effect of IL-6 inhibition in spondylarthritis. Joint Bone Spine. 2010 Dec;77(6):624-5. doi: 10.1016/j.jbspin.2010.09.011. Epub 2010 Oct 23.</mixed-citation><mixed-citation xml:lang="en">Wendling D, Bossert M, Prati C. Short-term effect of IL-6 inhibition in spondylarthritis. Joint Bone Spine. 2010 Dec;77(6):624-5. doi: 10.1016/j.jbspin.2010.09.011. Epub 2010 Oct 23.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Brulhart L, Nissen MJ, Chevallier P, Gabay C. Tocilizumab in a patient with ankylosing spondylitis and Crohn's disease refractory to TNF antagonists. Joint Bone Spine. 2010 Dec;77(6):625-6. doi: 10.1016/j.jbspin.2010.08.004. Epub 2010 Sep 20.</mixed-citation><mixed-citation xml:lang="en">Brulhart L, Nissen MJ, Chevallier P, Gabay C. Tocilizumab in a patient with ankylosing spondylitis and Crohn's disease refractory to TNF antagonists. Joint Bone Spine. 2010 Dec;77(6):625-6. doi: 10.1016/j.jbspin.2010.08.004. Epub 2010 Sep 20.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Shima Y, Tomita T, Ishii T, et al. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis. Mod Rheumatol. 2011 Aug;21(4):436-9. doi: 10.1007/s10165-011-0416-9. Epub 2011 Feb 9.</mixed-citation><mixed-citation xml:lang="en">Shima Y, Tomita T, Ishii T, et al. Tocilizumab, a humanized anti-interleukin-6 receptor antibody, ameliorated clinical symptoms and MRI findings of a patient with ankylosing spondylitis. Mod Rheumatol. 2011 Aug;21(4):436-9. doi: 10.1007/s10165-011-0416-9. Epub 2011 Feb 9.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Cohen JD, Ferreira R, Jorgensen C. Ankylosing spondylitis refractory to tumor necrosis factor blockade responds to tocilizumab. J Rheumatol. 2011 Jul;38(7): 1527. doi: 10.3899/jrheum.110265.</mixed-citation><mixed-citation xml:lang="en">Cohen JD, Ferreira R, Jorgensen C. Ankylosing spondylitis refractory to tumor necrosis factor blockade responds to tocilizumab. J Rheumatol. 2011 Jul;38(7): 1527. doi: 10.3899/jrheum.110265.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Koumakis E, Feydy A, Kahan A, Allanore Y. Interleukin 6 Blockade in Spondyloarthritis. J Rheumatol. 2012 May;39(5):1097-8; author reply 1098. doi: 10.3899/jrheum.110955.</mixed-citation><mixed-citation xml:lang="en">Koumakis E, Feydy A, Kahan A, Allanore Y. Interleukin 6 Blockade in Spondyloarthritis. J Rheumatol. 2012 May;39(5):1097-8; author reply 1098. doi: 10.3899/jrheum.110955.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004 Jun; 50(6):1761-9. doi: 10.1002/art.20303.</mixed-citation><mixed-citation xml:lang="en">Nishimoto N, Yoshizaki K, Miyasaka N, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum. 2004 Jun; 50(6):1761-9. doi: 10.1002/art.20303.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Courties A, Grateau G, Philippe P, et al. AA amyloidosis treated with tocilizumab: case series and updated literature review. Amyloid. 2015;22(2):84-92. doi: 10.3109/13506129.2014.1002031. Epub 2015 Jan 14.</mixed-citation><mixed-citation xml:lang="en">Courties A, Grateau G, Philippe P, et al. AA amyloidosis treated with tocilizumab: case series and updated literature review. Amyloid. 2015;22(2):84-92. doi: 10.3109/13506129.2014.1002031. Epub 2015 Jan 14.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Merashli M, De Marco G, Podgorski M, et al. Evidence of response to IL-6 inhibition in some cases of refractory spondyloarthritis associated peripheral synovitis. Ann Rheum Dis. 2016 Jul;75(7):1418-20. doi: 10.1136/annrheumdis-2016-209275. Epub 2016 Apr 8.</mixed-citation><mixed-citation xml:lang="en">Merashli M, De Marco G, Podgorski M, et al. Evidence of response to IL-6 inhibition in some cases of refractory spondyloarthritis associated peripheral synovitis. Ann Rheum Dis. 2016 Jul;75(7):1418-20. doi: 10.1136/annrheumdis-2016-209275. Epub 2016 Apr 8.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
